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Background: The number of donors from donation after circulatory determination of death (DCDD) has increased by at least 4-fold over the past decade. This study evaluated the association between the antecedent cardiac arrest status of controlled DCDD donors and the risk of delayed graft function (DGF)., Methods: Using data from the Australia and New Zealand Dialysis and Transplant, the associations between antecedent cardiac arrest status of DCDD donors before withdrawal of cardiorespiratory support, DGF, posttransplant estimated glomerular filtration rate (eGFR), and allograft loss were examined using adjusted logistic, linear mixed modeling, and cox regression, respectively. Among donors who experienced cardiac arrest, we evaluated the association between duration and unwitnessed status of arrest and DGF., Results: A total of 1173 kidney transplant recipients received DCDD kidneys from 646 donors in Australia between 2014 and 2019. Of these, 335 DCDD had antecedent cardiac arrest. Compared with recipients of kidneys from donors without antecedent cardiac arrest, the adjusted odds ratio (95% confidence interval) for DGF was 0.85 (0.65-1.11) among those with kidneys from donors with cardiac arrest. There was no association between antecedent cardiac arrest and posttransplant eGFR or allograft loss. The duration of cardiac arrest and unwitnessed status were not associated with DGF., Conclusions: This focused analysis in an Australian population showed that the allograft outcomes were similar whether DCDD donors had experienced a prior cardiac arrest, with no associations between duration or unwitnessed status of arrest and risk of DGF. This study thus provides important reassurance to transplant programs and the patients they counsel, to accept kidneys from donors through the DCDD pathway irrespective of a prior cardiac arrest., Competing Interests: G.W. is supported by an NHMRC Career Development Fellowship. The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Delayed graft function (DGF) is a form of acute kidney injury (AKI) and a common complication following kidney transplantation. It adversely influences patient outcomes increases the financial burden of transplantation, and currently, no specific treatments are available. In developing this form of AKI, activation of the renin-angiotensin system (RAS) has been proposed to play an important role. In this review, we discuss the role of RAS activation and its contribution to the pathophysiology of DGF following the different stages of the transplantation process, from procurement and ischemia to transplantation into the recipient and including data from experimental animal models. Deceased kidney donors, whether during cardiac or brain death, may experience activation of the RAS. That may be continued or further potentiated during procurement and organ preservation. Additional evidence suggests that during implantation of the kidney graft and reperfusion in the recipient, the RAS is activated and may likely remain activated, extrapolating from other forms of AKI where RAS overactivity is well documented. Of particular interest in this setting is the status of angiotensin-converting enzyme 2, a key RAS enzyme essential for the metabolism of angiotensin II and abundantly present in the apical border of the proximal tubules, which is the site of predominant injury in AKI and DGF. Interventions aimed at safely downregulating the RAS using suitable shorter forms of angiotensin-converting enzyme 2 could be a way to offer protection against DGF., Competing Interests: D.B. is a consultant for AstraZeneca, Renibus, and Advicenne; has ownership interest in Angiotensin Therapeutics Inc; received research funding from AstraZeneca, Feinberg Foundation, and the National Institutes of Health; and patents or royalties and founder of Angiotensin Therapeutics Inc. D.B. is the coinventor of patents: “Active Low Molecular Weight Variants of Angiotensin Converting Enzyme 2” and “Soluble ACE2 variants and uses therefore.” The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To assess the impact of CIT on living donor kidney transplantation (LDKT) outcomes in the UKLKSS versus outside the scheme., Background: LDKT provides the best treatment option for end-stage kidney disease patients. end-stage kidney disease patients with an incompatible living donor still have an opportunity to be transplanted through Kidney Exchange Programmes (KEP). In KEPs where kidneys travel rather than donors, cold ischaemia time (CIT) can be prolonged., Methods: Data from all UK adult LDKT between 2007 and 2018 were analysed., Results: 9969 LDKT were performed during this period, of which 1396 (14%) were transplanted through the UKLKSS, which we refer to as KEP. Median CIT was significantly different for KEP versus non-KEP (339 versus 182 minutes, P < 0.001). KEP LDKT had a higher incidence of delayed graft function (DGF) (2.91% versus 5.73%, P < 0.0001), lower 1-year (estimated Glomerular Filtration Rate (eGFR) 57.90 versus 55.25 ml/min, P = 0.04) and 5-year graft function (eGFR 55.62 versus 53.09 ml/min, P = 0.01) compared to the non-KEP group, but 1- and 5-year graft survival were similar. Within KEP, a prolonged CIT was associated with more DGF (3.47% versus 1.95%, P = 0.03), and lower graft function at 1 and 5-years (eGFR = 55 vs 50 ml/min, P = 0.02), but had no impact on graft survival., Conclusion: Whilst CIT was longer in KEP, associated with more DGF and lower graft function, excellent 5-year graft survival similar to non-KEP was found., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Tertiary hyperparathyroidism occurs in 25% to 50% of kidney-transplanted patients. Indication of parathyroidectomy is now discussed, since the calcimimetic agent, cinacalcet, is an alternate option. The effects of either of these treatments on graft function remain controversial, studied only in small cohorts showing either decrease or absence of modification. We performed a meta-analysis to evaluate the evolution of graft function after surgical or medical treatment., Methods: Studies assessing graft function in tertiary hyperparathyroidism after parathyroidectomy or cinacalcet introduction were enrolled into quantitative analysis using Pubmed, Embase, and Cochrane databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis reporting guidelines. Among 68 screened studies, 18 had no missing data and were included for statistical analyses. We performed random effect meta-analysis to determine changes in serum creatinine and estimated glomerular filtration rate., Results: Seven studies assessing the evolution of graft function 6 and/or 12 months after parathyroidectomy and 13 after administration of cinacalcet were included. Meta-analysis found no significant variations after parathyroidectomy in serum creatinine (6 studies, 314 patients) and estimated glomerular filtration rate (2 studies, 105 patients). No significant variation was found after administration of cinacalcet in serum creatinine (10 studies, 404 patients) and estimated glomerular filtration rate (6 studies, 149 patients). A significant heterogeneity between the studies (P < .01, Cochran's Q) was found., Conclusion: Meta-analysis shows that parathyroidectomy and cinacalcet do not significantly impair graft function in patients with tertiary hyperparathyroidism. However, the significant heterogeneity between selected studies, partially explained by the lack of consensual definition of tertiary hyperparathyroidism, limits the conclusions of all previously published series., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The aim of this study is to investigate whether or not delayed graft function (DGF) and pre-transplant sensitization have synergistic adverse effects on allograft outcome after deceased donor kidney transplantation (DDKT) using the Korean Organ Transplantation Registry (KOTRY) database, the nationwide prospective cohort. The study included 1359 cases between May 2014 and June 2019. The cases were divided into 4 subgroups according to pre-sensitization and the development of DGF post-transplant [non-pre-sensitized-DGF(-) (n = 1097), non-pre-sensitized-DGF(+) (n = 127), pre-sensitized-DGF(-) (n = 116), and pre-sensitized-DGF(+) (n = 19)]. We compared the incidence of biopsy-proven allograft rejection (BPAR), time-related change in allograft function, allograft or patient survival, and post-transplant complications across 4 subgroups. The incidence of acute antibody-mediated rejection (ABMR) was significantly higher in the pre-sensitized-DGF(+) subgroup than in other 3 subgroups. In addition, multivariable cox regression analysis demonstrated that pre-sensitization combined with DGF is an independent risk factor for the development of acute ABMR (hazard ratio 4.855, 95% confidence interval 1.499-15.727). Moreover, DGF and pre-sensitization showed significant interaction (p-value for interaction = 0.008). Pre-sensitization combined with DGF did not show significant impact on allograft function, and allograft or patient survival. In conclusion, the combination of pre-sensitization and DGF showed significant synergistic interaction on the development of allograft rejection after DDKT., (© 2021. The Author(s).)

Background: Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes., Methods: Primary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and GF contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II in mouse macrophages., Results: Doubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 1.02-1.2), whereas OPN decreased dcGF risk (aHR, 0.94; 95% CI, 0.88-1). UMOD:OPN ratio ≤3 strengthened the association, with reduced dcGF risk (aHR, 0.57; 0.41-0.80) with similar associations for GF, and in the test dataset. A ratio ≤3 was also associated with lower DGF (aOR, 0.73; 95% CI, 0.60-0.89) and higher 6-month eGFR (adjusted β coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II expression elucidating a possible mechanism behind UMOD's association with GF., Conclusions: UMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR, and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation., Competing Interests: S.G.M. supported by the American Heart Association (18CDA34110151) and Patterson Trust Fund. P.P.R. supported by epidemiology consulting from COHRDATA related to dialysis outcomes. This study received grant/research support from Merck, CVS and initiated grants from Merck to the University of Pennsylvania to support the THINKER (kidney), USHER (heart), and SHELTER (lung) trials of transplanting organs from donors with Hepatitis C into Hepatitis C negative recipients. It initiated grants from CVS to the University of Pennsylvania to support studies of medication adherence. I.E.H. received NIH grant support from NCATS (UL1TR002538 and KL2TR002539). T.M.E.-A. received grant support from NIDDK and US Department of Veterans Affairs. M.D.D. obtained the salary support from NIDDK. S.M. received grant/research support from NIH (NIDDK/NIAID/NIHMD/NIBIB) and consulting fees from Angion Pharmaceuticals. A.Z.R. received NDAs with Pliant Therapeutics and xMD Diagnostics, advisory board of Escala Therapeutics. C.R.P. received consulting fee from Renalytix and grant/research support from National Institute of Diabetes and Digestion and Kidney Diseases, National Heart, Lung, and Blood Institute and Data Safety and Monitoring Board of Genfit, Abbott. M.N.H. received grant support from NIH/NIDDK. The other authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Patients (20%-50%) undergoing renal transplantation experience acute kidney injury resulting in delayed graft function. ANG-3777 is an hepatocyte growth factor mimetic that binds to the c-MET receptor. In animal models, ANG-3777 decreases apoptosis, increases proliferation, and promotes organ repair and function., Methods: This was a randomized, double-blind, placebo-controlled, phase 2 trial of patients undergoing renal transplantation with <50 cc/h urine output for 8 consecutive hours over the first 24 hours posttransplantation, or creatinine reduction ratio <30% from pretransplantation to 24 hours posttransplantation. Subjects were randomized as 2:1 to 3, once-daily IV infusions of ANG-3777, 2 mg/kg (n = 19), or placebo (n = 9). Primary endpoint: time in days to achieve ≥1200 cc urine for 24 hours., Results: Patients treated with ANG-3777 were more likely to achieve the primary endpoint of 1200 cc urine for 24 hours by 28 days posttransplantation (83.3% versus 50% placebo; log-rank test: χ2 = 2.799, P = 0.09). Compared with placebo, patients in the ANG-3777 arm had larger increases in urine output; lower serum creatinine; greater reduction in C-reactive protein and neutrophil gelatinase-associated lipocalin; fewer dialysis sessions and shorter duration of dialysis; fewer hospital days; significantly less graft failure; and higher estimated glomerular filtration rate. Adverse events occurred in a similar percentage of subjects in both arms. Events per subject were twice as high in the placebo arm., Conclusions: There was an efficacy signal for improved renal function in subjects treated with ANG-3777 relative to placebo, with a good safety profile., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: During organ retrieval, surgeons estimate the degree of arteriosclerosis and this plays an important role in decisions on organ acceptance. Our study aimed to elucidate the association between macroscopic renal artery arteriosclerosis, donor kidney discard, and transplant outcome., Methods: We selected all transplanted and discarded kidneys in the Netherlands between January 1, 2000, and December 31, 2015, from deceased donors aged 50 y and older, for which data on renal artery arteriosclerosis were available (n = 2610). The association between arteriosclerosis and kidney discard, the relation between arteriosclerosis and outcome, and the correlation between macroscopic and microscopic arteriosclerosis were explored., Results: Macroscopic arteriosclerosis was independently associated with kidney discard (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.02-1.80; P = 0.03). Arteriosclerosis (any degree) was not significantly associated with delayed graft function (OR, 1.16; 95% CI, 0.94-1.43; P = 0.16), estimated glomerular filtration rate 1-y posttransplant (B, 0.58; 95% CI, -2.07 to 3.22; P = 0.67), and long-term graft survival (hazard ratio, 1.07; 95% CI, 0.86-1.33; P = 0.55). There was a significant association between mild arteriosclerosis and primary nonfunction (OR, 2.14; 95% CI, 1.19-3.84; P = 0.01). We found no correlation between macroscopic and histological arteriosclerosis, nor between histological arteriosclerosis and transplant outcome., Conclusions: Macroscopic arteriosclerosis of the renal artery was independently associated with kidney discard and somewhat associated with primary nonfunction posttransplant. However, there was no effect of arteriosclerosis on delayed graft function, estimated glomerular filtration rate at 1 y, or long-term graft survival. Our results are valid only after inevitable exclusion of discarded kidneys that had on average more arteriosclerosis. Hence, conclusions should be interpreted in the light of this potential bias.

Background: The effects of delayed graft function on long-term kidney allograft outcomes are poorly defined among simultaneous liver and kidney transplant recipients., Methods: We analyzed data of all simultaneous liver and kidney recipients transplanted at the University of Wisconsin between 2010 and 2017. Risk factors for the development of delayed graft function, kidney graft failure, and patient mortality were outcomes of interest., Results: There were a total of 60 simultaneous liver and kidney recipients; 28 (47%) had delayed graft function. After adjustment for multiple variables, we found that pretransplant dialysis >6 weeks (hazard ratio [HR] = 5.6, 95% CI: 1.23-25.59, P = .02), pretransplant albumin <3 g/dL (HR = 5.75, 95% CI: 1.76-16.94, P = .003), and presence of pretransplant diabetes (HR = 2.5, 95% CI: 0.97-4.77, P = .05) were significantly associated with delayed graft function. Multivariate analysis showed that pretransplant albumin <3 (HR = 4.86, 95% CI: 1.07-22.02, P = .02) was associated with a higher risk of all-cause kidney allograft failure, whereas the duration of delayed graft function (HR = 1.07 per day, 95% CI: 1.01-1.14, P = .01) was associated with a higher risk of death-censored kidney allograft failure. The presence of delayed graft function was not associated with all-cause or death-censored kidney or liver allograft failure. Similarly, the presence of delayed graft function was not associated with patient mortality., Conclusion: The incidence of delayed graft function was high in simultaneous liver and kidney recipients. However, with appropriate management, delayed graft function may not have a negative impact on patient or kidney allograft survival.

Background: Due to the current high demand for transplant tissue, an increasing proportion of kidney donors are considered extended criteria donors, which results in a higher incidence of delayed graft function (DGF) in organ recipients. Therefore, it is important to fully investigate the risk factors of DGF, and establish a prediction system to assess donor kidney quality before transplantation. Methods: A total of 333 donation after cardiac death kidney transplant recipients were included in this retrospective study. Both univariate and multivariate analyses were used to analyze the risk factors of DGF occurrence. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of variables on DGF posttransplant. Results: The donor clinical scores, kidney histopathologic Remuzzi scores and hypothermic mechanical perfusion (HMP) parameters (flow and resistance index) were all correlated. 46 recipients developed DGF postoperatively, with an incidence of 13.8% (46/333). Multivariate logistic regression analysis of the kidney transplants revealed that the independent risk factors of DGF occurrence post-transplantation included donor score (OR = 1.12, 95% CI 1.06-1.19, p  < 0.001), Remuzzi score (OR = 1.21, 95% CI 1.02-1.43, p  = 0.029) and acute tubular injury (ATI) score (OR = 4.72, 95% CI 2.32-9.60, p  < 0.001). Prediction of DGF with ROC curve showed that the area under the curve was increased to 0.89 when all variables (donor score, Remuzzi score, ATI score and HMP resistance index) were considered together. Conclusions: Combination of donor clinical information, kidney pre-implant histopathology and HMP parameters provide a more accurate prediction of DGF occurrence post-transplantation than any of the measures alone.

Background: Consider a theoretical situation in which 2 patients with similar baseline characteristics receive a kidney transplant on the same day: 1 from a standard criteria deceased donor, the other from a living donor. Which kidney transplant will last longer?, Methods: We conducted a population-based cohort study using linked administrative healthcare databases from Ontario, Canada, from January 1, 2005, to March 31, 2014, to evaluate several posttransplant outcomes in individuals who received a kidney transplant from a standard criteria deceased donor (n = 1523) or from a living donor (n = 1373). We used PS weighting using overlap weights, a novel weighting method that emphasizes the population of recipients with the most overlap in baseline characteristics., Results: Compared with recipients of a living donor, the rate of all-cause graft failure was not statistically higher for recipients of a standard criteria deceased donor (hazard ratio, 1.1; 95% confidence interval [CI], 0.8-1.6). Recipients of a standard criteria deceased donor, compared with recipients of a living donor had a higher rate of delayed graft function (23.6% versus 18.7%; odds ratio, 1.3; 95% CI, 1.0-1.6) and a longer length of stay for the kidney transplant surgery (mean difference, 1.7 d; 95% CI, 0.5-3.0)., Conclusions: After accounting for many important donor and recipient factors, we failed to observe a large difference in the risk of all-cause graft failure for recipients of a standard criteria deceased versus living donor. Some estimates were imprecise, which meant we could not rule out the presence of smaller clinically important effects.

Introduction: The concept of anesthesia, in which kidney perfusion is optimized, the use of nephrotoxic drugs is avoided, and general anesthesia with protective and preconditioning properties of the graft is applied, is a key element of the therapeutic strategy in kidney transplantation (KTx)., Material and Method: A total of 86 patients (mean age: 49.4 ± 14.0 years, 66% men) with end-stage renal disease who underwent KTx between 2012 and 2015 were included in this retrospective study. Our aim was to assess the effect of oxygen content in arterial blood and selected hemodynamic parameters on the graft function and the occurrence of delayed graft failure., Results: No differences were found in baseline characteristics, indication for transplantation, and surgical technique used among study population. No correlation was found between oxygen delivery exponents and both standard markers of renal function and new biochemical markers (eg, IL-18, clusterin, and neutrophil gelatinase-associated lipocalin [NGAL])., Discussion: In our study, hemodynamic parameters measured at scheduled intervals did not exceed the physiological range, which might have been the reason for the lack of correlation between the function of graft and the described hemodynamic conditions. At the same time, in the observed ranges of perfusion pressure during optimization of the oxygen content, no correlations were found with the postoperative function of the transplanted kidney. That observation could be a valuable conclusion for reducing the tendency of maintaining high blood pressure with the abuse of catecholamines, especially vasoconstrictors, and volume therapy, whose negative effect on tissue perfusion is unequivocal., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Mannitol and furosemide have been used as diuretics intraoperatively to facilitate early renal allograft function and reduce delayed graft function. As the evidence of any efficacy of these agents is limited, we sought to characterize the use of diuretics among transplant surgeons., Methods: An anonymous online survey was sent to all Canadian transplant programs where kidney transplants are routinely performed. Questions were related to the use and indications for mannitol and furosemide. Responses were collected and analyzed as counts and percentages of respondents. We used χ2 analysis to assess the relationship between demographic factors and survey responses., Results: Thirty-five surgeons completed the survey (response rate 50%). Seventy per cent of respondents reported performing 26 or more transplants per year, 88% had formal transplant fellowship training and 67% indicated that they currently train fellows. Only 24% and 12% reported believing that delayed graft function is reduced by mannitol and furosemide use, respectively. However, 73% routinely gave mannitol to patients and 53% routinely gave furosemide. The most common justification given for mannitol use was to induce diuresis (54%); 37% of respondents reported using mannitol because of training dogma. Likewise, 57% used furosemide for diuresis, with 23% reporting that their use of this agent was based on dogma. No relationship emerged between fellowship training, case volume or training program status and the use of any agent. Interestingly, 71% of respondents indicated that a randomized controlled trial evaluating the utility of intraoperative diuretics is needed and that they were interested in participating in such a trial., Conclusion: Use of intraoperative diuretics and the rationale for their use vary among surgeons. A substantial proportion of surgeons use these medications on the basis of dogma alone. A randomized controlled trial is needed to clarify the role of intraoperative diuretics in kidney transplant surgery.

Although over 90 000 people are on the kidney transplant waitlist in the United States, some kidneys that are viable for transplantation are discarded. Transplant surgeons are more likely to discard deceased donors with acute kidney injury (AKI) versus without AKI (30% versus 18%). AKI is defined using changes in creatinine from baseline. Transplant surgeons can use DonorNet data, including admission, peak, and terminal serum creatinine, and biopsy data when available to differentiate kidneys with AKI from those with chronic injury. Although chronic kidney disease is associated with reduced graft survival, an abundance of literature has demonstrated similar graft survival for deceased donors with AKI versus donors without AKI. Donors with AKI are more likely to undergo delayed graft function but have similar long-term outcomes as donors without AKI. The mechanism for similar graft survival is unclear. Some hypothesized mechanisms include (1) ischemic preconditioning; (2) posttransplant and host factors playing a greater role in long-term survival than donor factors; and (3) selection bias of transplanting only relatively healthy donor kidneys with AKI. Existing literature suggests transplanting more donor kidneys with stage 1 and 2 AKI, and cautious utilization of stage 3 AKI donors, may increase the pool of viable kidneys. Doing so can reduce the number of people who die on the waitlist by over 500 every year.

Background: Constrictive pericarditis is easily overlooked and can lead to severe problems in hemodynamics and end-organ perfusion, in our patient leading to 98 days of anuria after living kidney transplantation. This was completely reversible after pericardectomy., Case Presentation: A 43-year-old female caucasian patient received a living kidney donation from her mother. She had developed end-stage renal disease 2 years prior due to nephrotic syndrome linked to graft-versus-host disease after allogenic stem-cell transplantation for aplastic anemia. The graft showed insufficient function already in the early postoperative phase. Dialysis was paused after surgery, but the patient developed hypervolemia with ascites and edema in the lower extremities. Doppler ultrasonography showed scarce perfusion, with intrarenal arterial waveforms without end-diastolic flow. The venous perfusion profiles showed pulsatile retrograde flow. There was no identifiable reason for a primary vascular perfusion problem on ultrasonography or transplant kidney angiography. Kidney transplant biopsy revealed no rejection but extensive acute tubular necrosis. Three weeks after transplantation, the patient developed an acute anuric graft failure caused by severe cardiac decompensation. Echocardiography revealed a previously unnoticed constrictive pericarditis, which could be confirmed in a cardio computed tomography scan. The constrictive pericarditis had not been apparent on previous x-rays, computed tomography scans, or echocardiographies, including those for transplantation evaluation. Conservative management of the constrictive pericarditis was not successful and the graft remained anuric. Eventually, the patient underwent pericardectomy 16 weeks after kidney transplantation. Shortly after surgery, the graft started urine production again, which significantly increased within a few days. The clearance improved and 2 weeks later, the patient was free from dialysis., Conclusions: This case illustrates that special attention should be given to the pericardium during transplant evaluation, especially for patients who previously underwent stem-cell transplantations, chemotherapy or radiation.

Background: The delayed graft function (DGF) in kidney transplantation (KT) is a risk factor for long-term poor graft survival. The pathogenesis is multifactorial but mainly related to an ischemia-reperfusion injury. However, the graft hemodynamics have been recently identified as a key aspect for early DGF risk assessment and potential therapeutic intervention., Methods: A pilot study on 20 single kidney grafts from donor after brain death with intraoperative measurement of graft arterial flowmetry, 30 minutes after reperfusion. Exclusion criteria were grafts with multiple arteries or severe atherosclerosis of the recipient's external iliac artery., Results: KT recipients with DGF (n = 4, 20%) were homogenous with controls (n = 16) in terms of cold ischemia time, donor age, recipients' hemodynamic parameters, renal artery, and recipients' external iliac artery diameters. Nonetheless, at transplant, the kidney grafts that developed DGF were characterized by a significantly higher renal artery resistive index (DGF vs no-DGF 0.96 ± 0.04 vs 0.77 ± 0.13, P = .02), as well as lower flow extraction rate (24.8% ± 11.8 vs 59.2% ± 21.1, P < .01)., Conclusions: Intraoperative arterial graft flowmetry seems to be an effective tool to identify grafts at high risk of DGF., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Better preservation strategies for the storage of donation after circulatory death grafts are essential to improve graft function and to increase the kidney donor pool. We compared continuous normothermic ex vivo kidney perfusion (NEVKP) with hypothermic anoxic machine perfusion (HAMP) and static cold storage (SCS) in a porcine kidney autotransplantation model., Methods: Porcine kidneys were exposed to 30 minutes of warm ischemia and then reimplanted following either 16 hours of either SCS, HAMP (LifePort 1.0), or NEVKP before autotransplantation (n = 5 per group). The contralateral kidney was removed. Animals were followed for 8 days., Results: Grafts preserved by NEVKP demonstrated improved function with more rapid recovery compared with HAMP and SCS (mean peak serum creatinine: 3.66 ± 1.33 mg/dL [postoperative d 1 [(POD1)], 8.82 ± 3.17 mg/dL [POD2], and 12.90 ± 2.19 mg/dL [POD3], respectively). The NEVKP group demonstrated significantly increased creatinine clearance calculated on POD3 (63.6 ± 19.0 mL/min) compared with HAMP (13.5 ± 10.3 mL/min, P = 0.001) and SCS (4.0 ± 2.6 mL/min, P = 0.001). Histopathologic injury scores on POD8 were lower in both perfused groups (NEVKP and HAMP, score: 1-1.5) compared with SCS (score: 1-3, P = 0.3), without reaching statistical significance., Conclusions: NEVKP storage significantly improved early kidney function compared with both cold preservation strategies, although HAMP also demonstrates improvement over SCS. NEVKP may represent a novel, superior preservation option for donation after circulatory death renal grafts compared with conventional hypothermic methods.

Background: The benefits of cold pulsatile machine perfusion (MP) for the storage and transportation of kidneys donated after circulatory death are disputed. We conducted a UK-based multicenter, randomized controlled trial to compare outcomes of kidneys stored with MP versus static cold storage (CS)., Methods: Fifty-one pairs of kidneys donated after circulatory death were randomly allocated to receive static CS or cold pulsatile MP. The primary endpoint, delayed graft function, was analyzed by "intention-to-treat" evaluation., Results: There was no difference in the incidence of delayed graft function between CS and MP (32/51 (62.8%) and 30/51 (58.8%) P = 0.69, respectively), although the trial stopped early due to difficulty with recruitment. There was no difference in the incidence of acute rejection, or in graft or patient survival between the CS and MP groups. Median estimated glomerular filtration rate at 3 months following transplantation was significantly lower in the CS group compared with MP (CS 34 mL/min IQR 26-44 vs MP 45 mL/min IQR 36-60, P = 0.006), although there was no significant difference in estimated glomerular filtration rate between CS and MP at 12 months posttransplant., Conclusions: This study is underpowered, which limits definitive conclusions about the use of MP, as an alternative to static CS. It did not demonstrate that the use of MP reduces the incidence of delayed graft function in donation after circulatory death kidney transplantation.

Background: An elevated terminal creatinine is frequently used as a reason for organ refusal in pediatric kidney transplantation. There is increasing evidence that adults who receive kidneys from donors with moderate to severe acute kidney injury (AKI) have similar outcomes to recipients who receive kidneys from donors with none to mild AKI., Methods: We used the Scientific Registry of Transplant Recipients to determine how many pediatric kidney transplant recipients developed delayed graft function (DGF) between 2000 and 2010., Results: When stratified by the donor terminal creatinine, there was no significant difference in the recipient discharge creatinine or the likelihood of developing DGF. In a logistic regression model, older donor age, male donors, and a longer cold ischemia time but not donor terminal creatinine were independent predictors of DGF. There were very few graft loss events documented in this study., Conclusions: Our results are in agreement with previously published data; a high donor terminal creatinine is not significantly associated with DGF in pediatric renal transplant recipients. Additional studies investigating the risk of rejection and long-term graft function are needed before adopting the practice of accepting kidneys with moderate to severe AKI in pediatric kidney transplant recipients.

Background: Delayed graft function (DGF) is associated with inferior posttransplant outcomes in kidney transplantation. Given these adverse outcomes, we sought to determine the incidence, unique risk factors, and posttransplant outcomes for simultaneous liver kidney (SLK) transplant recipients developing DGF., Methods: We studied 6214 adult SLK recipients from March 2002 to February 2017 using the Scientific Registry of Transplant Recipients. We determined associations between risk factors and DGF using Poisson multivariate regression and between DGF and graft failure and mortality using Cox proportional hazard analysis., Results: The overall rate of DGF was 21.8%. Risk factors for DGF in the hepatitis C virus (HCV)-negative recipient population included pretransplant dialysis (adjusted incident rate ratio [aIRR] 3.26, P = 0.004), donor body mass index (aIRR 1.25 per 5 kg/m, P = 0.01), and transplantation with a donation after circulatory death (aIRR 5.38, P = 0.001) or imported donor organ (regional share aIRR 1.69, P = 0.03; national share aIRR 4.82, P < 0.001). DGF was associated with a 2.6-fold increase in kidney graft failure (adjusted hazard ratio [aHR] 2.63, P < 0.001), 1.6-fold increase in liver graft failure (aHR 1.62, P < 0.001), and 1.6-fold increase in mortality (aHR 1.62, P < 0.001)., Conclusions: In HCV-negative SLK recipients, recipient pretransplant dialysis and components of kidney graft quality comprise significant risk factors for DGF. Regardless of HCV status, DGF is associated with inferior posttransplant outcomes. Understanding these risk factors during clinical decision-making may improve prevention of DGF and may represent an opportunity to improve posttransplant outcomes.

Background and Objectives: Delayed graft function is related to ischemia-reperfusion injury and may be complement dependent. We previously reported from a randomized, placebo-controlled trial that treatment with C1 esterase inhibitor was associated with a shorter duration of delayed graft function and higher eGFR at 1 year. Here, we report longer-term outcomes from this trial., Design, Setting, Participants, & Measurements: This is a post hoc analysis of a phase 1/2, randomized, controlled trial enrolling 70 recipients of deceased donor kidney transplants at risk for delayed graft function (NCT02134314). Subjects were randomized to receive C1 esterase inhibitor 50 U/kg ( n =35) or placebo ( n =35) intraoperatively and at 24 hours. The cumulative incidence functions method was used to compare graft failure and death over 3.5 years. eGFR slopes were compared using a linear mixed effects model., Results: Three deaths occurred among C1 esterase inhibitor-treated patients compared with none receiving placebo. Seven graft failures developed in the placebo group compared with one among C1 esterase inhibitor-treated recipients; the cumulative incidence of graft failure was lower over 3.5 years among C1 esterase inhibitor-treated recipients compared with placebo ( P =0.03). Although no difference in eGFR slopes was observed between groups ( P for group-time interaction =0.12), eGFR declined in placebo-treated recipients (-4 ml/min per 1.73 m 2 per year; 95% confidence interval, -8 to -0.1) but was stable in C1 esterase inhibitor-treated patients (eGFR slope: 0.5 ml/min per 1.73 m 2 per year; 95% confidence interval, -4 to 5). At 3.5 years, eGFR was 56 ml/min per 1.73 m 2 (95% confidence interval, 42 to 70) in the C1 esterase inhibitor group versus 35 ml/min per 1.73 m 2 (95% confidence interval, 21 to 48) in the placebo group, with an estimated mean eGFR difference of 21 ml/min per 1.73 m 2 (95% confidence interval, 2 to 41 ml/min per 1.73 m 2 )., Conclusions: Treatment of patients at risk for ischemia-reperfusion injury and delayed graft function with C1 esterase inhibitor was associated with a lower incidence of graft failure., (Copyright © 2020 by the American Society of Nephrology.)

Background: Urological obstructive complications (UOC) affect up to 15% of kidney transplants (KTX). Most cases are excluded by ultrasonography (US); however, accuracy may be limited in the early transplant phase. Features of acute tubular injury (ATI) in KTX biopsy may be informative but histological features indicating UOC are ill defined. Tubular ectasia (TE) was shown to be associated with UOC in experimental data. We evaluated the association of histomorphological features, particularly TE, with occult (=without relevant hydronephrosis in US) UOC and renal outcomes., Methods: We included all recipients with an early indication biopsy (976 of 1537 consecutive KTX). The biopsy finding of TE classified as "suspicious of UOC" was compared with the following endpoints: delayed graft function, estimated glomerular filtration rate, and occult UOC. Additionally, histopathological features of ATI were reevaluated by a single pathologist to increase diagnostic accuracy., Results: Fifty-eight (5.9%) patients presented with TE, which was not related to delayed graft function or estimated glomerular filtration rate. Forty percent of patients had a UOC (most frequently ureteral stenosis) close to biopsy. Comparing these biopsies to matched controls, TE was significantly associated with UOC (odds ratio 2.69; P = 0.018). After histopathological reevaluation of these biopsies including additional features of ATI, we developed a final multivariate model with a highly significant relationship to UOC (Receiver operating characteristic-area under the curve: 0.77; P = 0.001). The model provides a specificity of 78% and negative predictive value of 73%., Conclusions: TE together with additional signs of ATI indicates occult UOC. This histological phenotype should trigger more detailed evaluation for UOC when there is no evidence of relevant hydronephrosis in the ultrasonography.

Objective: To explore putative different impacts of delayed graft function (DGF) on long-term graft survival in kidneys donated after brain death (DBD) and circulatory death (DCD)., Background: Despite a 3-fold higher incidence of DGF in DCD grafts, large studies show equivalent long-term graft survival for DBD and DCD grafts. This observation implies a differential impact of DGF on DBD and DCD graft survival. The contrasting impact is remarkable and yet unexplained., Methods: The impact of DGF on DBD and DCD graft survival was evaluated in 6635 kidney transplants performed in The Netherlands. DGF severity and functional recovery dynamics were assessed for 599 kidney transplants performed at the Leiden Transplant Center. Immunohistochemical staining, gene expression profiling, and Ingenuity Pathway Analysis were used to identify differentially activated pathways in DBD and DCD grafts., Results: While DGF severely impacted 10-year graft survival in DBD grafts (HR 1.67; P < 0.001), DGF did not impact graft survival in DCD grafts (HR 1.08; P = 0.63). Shorter dialysis periods and superior posttransplant eGFRs in DBD grafts show that the differential impact was not caused by a more severe DGF phenotype in DBD grafts. Immunohistochemical evaluation indicates that pathways associated with tissue resilience are present in kidney grafts. Molecular evaluation showed selective activation of resilience-associated pathways in DCD grafts., Conclusions: This study shows an absent impact of DGF on long-term graft survival in DCD kidneys. Molecular evaluation suggests that the differential impact of DGF between DBD and DCD grafts relates to donor-type specific activation of resilience pathways in DCD grafts.

Background: The hypothermic machine perfusion reduces delayed graft function after kidney transplant and allows, to some extent, predicting early graft function. However, it is difficult to identify exact perfusion criteria with which to exclude kidneys from transplant or modify post-transplant care. The aim of this study was to analyze whether renal resistance during the fourth hour of hypothermic machine perfusion is useful in the prediction of graft survival and acute rejection., Patients and Methods: Data on pretransplant hypothermic machine perfusion parameters of 407 transplanted kidneys were available. Receiver operating characteristic curve analysis was performed to find an optimal cutoff value of ratio for predicting a higher risk class of considered group of patients. According to this, patients were divided into 2 groups: those who received kidneys with renal resistance lower than 0.19 mm Hg/mL/min (R1; n = 187) and those who received kidneys with renal resistance equal to or higher than 0.19 mm Hg/mL/min (R2; n = 220). Within R2, we additionally analyzed 2 subgroups: patients who received induction therapy (R2-Ind+; n = 124) and those who did not received induction therapy (R2-Ind-; n = 96)., Results: Acute rejection in R1 within 1 month post transplant was 2-fold lower compared with R2 and was 6.4% vs 13.1% (P = .03), respectively. One-year graft survival was higher in R1 compared with R2 and was 94.6% vs 88.5% (P = .03), respectively. Acute rejection in the R2-Ind+ subgroup within 1 month post transplant was 2.46-fold lower compared with the R2-Ind- subgroup and was 8% vs 19.7% (P = .01), respectively., Conclusion: Immunosuppression treatment after transplant should be adjusted to perfusion parameters., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Our aim was to evaluate which histologic lesions in a donor kidney were associated with graft function up to 5 years and with its dynamics., Materials and Methods: We retrospectively investigated the association between acute and chronic individual histologic lesions and composite scores in preimplant and postreperfusion biopsies from deceased-donor (n = 101) and living-donor (n = 29) kidneys with initial graft function and function at discharge, at 6 months, and at 5 years and slopes of estimated glomerular filtration rate from discharge to 6 months and from 6 months to 5 years., Results: A high frequency of chronic and acute histologic lesions in donor kidneys is characteristic of our population of donors with high cardiovascular risk. Glomerulitis in preimplant biopsies predicted delayed graft function. Arteriolar hyalinosis predicted impaired initial graft function. Arteriolar hyalinosis and arteriosclerosis both predicted lower estimated glomerular filtration rate at discharge and ≥ 25% drop in function after 6 months. Glomerulosclerosis affected the estimated glomerular filtration rate at discharge and at 6 months; percentage of changed glomeruli predicted lower function at discharge and at 5 years. Glomerular thrombi in preimplant and postreperfusion biopsies predicted negative slope in estimated glomerular filtration rate from discharge to 6 months and a ≥ 25% drop in function after 6 months, respectively. Fibrinoid necrosis in glomeruli in preimplant biopsies predicted decline in function of ≥ 5 mL/min/1.73m² every year after 6 months. Chronic and total preimplant and posttransplant Banff scores predicted lower estimated glomerular filtration rate at discharge and at 6 months, with ≥ 25% drop in function after 6 months., Conclusions: Intraoperative biopsies are important in identifying patients at risk for worse graft function, especially concerning absence of gain of function early after transplant and loss of function late after transplant.

Introduction: Delayed graft function (DGF) has a significant impact on kidney transplantation outcome. One of the underlying pivotal mechanisms is organ preservation and associated hypothermia and biochemical alteration., Areas Covered: This paper focuses on organ preservation and its clinical consequences and describes 1. A comprehensive presentation of the pathophysiological mechanism involved in delayed graft function development; 2. The impact on endothelial cells and microvasculature integrity and the consequences on transplanted organ outcome; 3. The reassessment of dynamic organ preservation motivated by the growing use of extended criteria donors and the interest in the potential of normothermia; 4. The role of oxygenation during dynamic preservation; and 5. Novel oxygen carriers and their proof of concept in transplantation, among which M101 (HEMO 2 life®) is currently the most extensively investigated., Expert Opinion: Metabolic disturbances and imbalance of oxygen supply during preservation highlight the importance of providing oxygen. Normothermia, permitted by recent advances in machine perfusion technology, appears to be the leading edge of preservation technology. Several oxygen transporters are compatible with normothermia; however, only M101 also demonstrates compatibility with standard hypothermic preservation.

Exhaustion of vascular accesses is a major complication in patients undergoing hemodialysis, especially in pediatric setting. We report the case of a boy treated for loss of hemodialysis access after a combined liver-kidney transplantation and transient renal dysfunction. An interventional dilatation of calcific superior vena cava allowed to insert a stable central venous line for dialysis until full graft recovery. Careful management of central lines allows to spare the main vessels and reduces the need for unusual accesses.

Background: Donor organ quality is a key determinant of graft outcomes in deceased donor kidney transplantation (DDKT). The predictive values of baseline histopathology and several clinical scoring systems for long-term graft outcomes have been evaluated, but the results remain controversial., Materials and Methods: We screened 167 patients who underwent DDKT at Ulsan University Hospital from April 2003 to June 2016. Among them, 66 patients who underwent baseline kidney biopsy and whose kidney donor risk index (KDRI) was available were included in this analysis. All baseline biopsies were rescored according to the updated Banff classification., Results: Median follow-up was 22 months. Mean age of recipients and donors was 51.4 and 44.7 years, respectively. Mean KDRI was 1.40 ± 0.44. During follow-up, delayed graft function and biopsy-proven acute rejection (BPAR) developed in 7 and 11 patients, respectively. Graft failure occurred in 2 patients. In Cox regression analysis, interstitial fibrosis/tubular atrophy (IFTA) (hazard ratio (HR) = 3.59; p = 0.049) was a significant risk factor for BPAR. In multivariate linear regression, age (standardized β (SB) = -0.282; p = 0.002), BPAR (SB = -0.406; p < 0.001), KDRI (SB = -0.277; p = 0.003), and IFTA (SB = -0.298; p = 0.001) were significant predictors of last-visit estimated glomerular filtration rate (eGFR)., Conclusion: Several clinical and pathologic parameters, such as KDRI and IFTA, may be helpful for predicting long-term graft outcomes, including BPAR and last-visit eGFR, in DDKT.
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The impact of the duration of delayed graft function (DGF) on graft survival is poorly characterized in controlled donation after circulatory death (DCD) donor kidney transplantation. A retrospective analysis was performed on 225 DCD donor kidney transplants between 2011 and 2016. When patients with primary nonfunction were excluded (n = 9), 141 recipients (65%) had DGF, with median (IQR) duration of dialysis dependency of 6 (2-11.75) days. Longer duration of dialysis dependency was associated with lower estimated glomerular filtration rate at 1 year, and a higher rate of acute rejection. On Kaplan-Meier analysis, the presence of DGF was associated with lower graft survival (log-rank test P = 0.034), though duration of DGF was not (P = 0.723). However, multivariable Cox regression analysis found that only acute rejection was independently associated with lower graft survival [HR (95% CI) 4.302 (1.617-11.450); P = 0.003], whereas the presence of DGF and DGF duration were not. In controlled DCD kidney transplantation, DGF duration itself may not be independently associated with graft survival; rather, it may be that acute rejection associated with prolonged DGF is the poor prognostic factor., (© 2019 Steunstichting ESOT.)

Background: Kidney delayed graft function (kDGF) remains a challenging problem following simultaneous liver and kidney transplantation (SLKT) with a reported incidence up to 40%. Given the scarcity of renal allografts, it is crucial to minimize the development of kDGF among SLKT recipients to improve patient and graft outcomes. We sought to assess the role of preoperative recipient and donor/graft factors on developing kDGF among recipients of SLKT., Methods: A retrospective review of 194 patients who received SLKT in the period from January 2004 to March 2017 in a single center was performed to assess the effect of preoperative factors on the development of kDGF., Results: Kidney delayed graft function was observed in 95 patients (49%). Multivariate analysis revealed that donor history of hypertension, cold static preservation of kidney grafts [versus using hypothermic pulsatile machine perfusion (HPMP)], donor final creatinine, physiologic MELD, and duration of delay of kidney transplantation after liver transplantation were significant independent predictors for kDGF. kDGF is associated with worse graft function and patient and graft survival., Conclusions: Kidney delayed graft function has detrimental effects on graft function and graft survival. Understanding the risks and combining careful perioperative patient management, proper recipient selection and donor matching, and graft preservation using HPMP would decrease kDGF among SLKT recipients., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The increasing use of extended criteria organs to meet the demand for kidney transplantation raises an important question of how the severity of early ischaemic injury influences long-term outcomes. Significant acute ischaemic kidney injury is associated with delayed graft function, increased immune-associated events and, ultimately, earlier deterioration of graft function. A comprehensive understanding of immediate molecular events that ensue post-ischaemia and their potential long-term consequences are key to the discovery of novel therapeutic targets. Acute ischaemic injury primarily affects tubular structure and function. Depending on the severity and persistence of the insult, this may resolve completely, leading to restoration of normal function, or be sustained, resulting in persistent renal impairment and progressive functional loss. Long-term effects of acute renal ischaemia are mediated by several mechanisms including hypoxia, HIF-1 activation, endothelial dysfunction leading to vascular rarefaction, sustained pro-inflammatory stimuli involving innate and adaptive immune responses, failure of tubular cells to recover and epigenetic changes. This review describes the biological relevance and interaction of these mechanisms based on currently available evidence.

Background: Thirty-day readmission rates (early hospital readmission, EHR) are an important benchmark for quality improvement. Nationally, patients undergoing renal transplantation incur a 31% EHR rate. While national databases provide useful data, the impact of EHR on individual centers has received little attention. We proposed that an institutional review of EHR after renal transplantation may provide a benchmark for individual transplant programs and identify modifiable program-specific issues to reduce EHR., Methods: We reviewed 269 consecutive kidney transplant recipients over a five-year period (2012-2016). Early hospital readmission was modeled using generalized linear modeling assuming a binary distribution., Results: About 21% of patients were readmitted within 30 days. Deceased kidney donation (DD), delayed graft functioning (DGF), anti-thymocyte globulin (ATG) induction, diabetes, public insurance, weekend discharge, and low glomerular filtration rate (eGFR) at discharge were all identified as risk factors for readmission. Early hospital readmission was not correlated with risk of death (5.4% at 44 months: HR 2.2 (95% CI [0.7, 6.6]; P = 0.1473) or graft loss., Conclusions: EHR after renal transplantation is common. Certain factors may predict an increased risk for EHR. A multi-disciplinary approach to discharge planning may limit some EHR, but most complications and adverse events are unpredictable and require hospital-level of care., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To analyze pre-transplantation and early postoperative factors affecting post-transplantation urine output and develop a predictive nomogram., Patients and Methods: Retrospective analysis of non-preemptive first transplanted adult patients between 2001-2016. The outcomes were hourly diuresis in mL/Kg in the 1st (UO1) and 8th (UO8) postoperative days (POD). Predictors for both UO1 and UO8 were cold ischemia time (CIT), patient and donor age and sex, HLA I and II compatibility, pre-transplantation duration of renal replacement therapy (RRT), cause of ESRD (ESRD) and immunosuppressive regimen. UO8 predictors also included UO1, 1st/0th POD plasma creatinine concentration ratio (Cr1/0), and occurrence of acute cellular rejection (AR). Multivariable linear regression was employed to produce nomograms for UO1 and UO8., Results: Four hundred and seventy-three patients were included, mostly deceased donor kidneys' recipients (361, 70.4%). CIT inversely correlated with UO1 and UO8 (Spearman's p=-0.43 and -0.37). CR1/0 inversely correlated with UO8 (p=-0.47). On multivariable analysis UO1 was mainly influenced by CIT, with additional influences of donor age and sex, HLA II matching and ESRD. UO1 was the strongest predictor of UO8, with significant influences of AR and ESRD., Conclusions: The predominant influence of CIT on UO1 rapidly wanes and is replaced by indicators of functional recovery (mainly UO1) and allograft's immunologic acceptance (AR absence). Mean absolute errors for nomograms were 0.08 mL/Kg h (UO1) and 0.05 mL/Kg h (UO8)., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Background: Temporary portocaval shunt has a positive impact on short-term outcomes after liver transplantation. An alternative to temporary portocaval shunt is a distal passive decompression through mesenterico-saphenous shunt. The purpose of this study was to compare outcomes of these two types of surgical portosystemic shunt and discuss their respective place during the anhepatic phase., Methods: Patients transplanted with portal decompression during a 4-year period were included. Patients were compared according to two types of surgical decompression techniques: temporary portocaval shunt (n = 44) and mesenterico-saphenous shunt (n = 77). Spontaneous >5-mm portosystemic shunts were described as absent, nonpersistent, distal, or proximal. Intraoperative portal pressure variations and inhospital course were compared between the two groups, with special attention on the impact of competing spontaneous and surgical shunts., Results: Mesenterico-saphenous shunt and temporary portocaval shunt showed a comparable hemodynamic efficiency, with no significant difference in terms of portal pressure variations. We found no significant difference in terms of reperfusion syndrome (P = .956), transfusion rate (P = .575), renal failure (P = .239) nor early allograft dysfunction (P = .976). There was a significantly higher risk of early allograft dysfunction when competing surgical and spontaneous shunts were used (P = .002) with a lesser hemodynamic efficiency (analysis of variance test; P = .04)., Conclusion: Portacaval or mesenterico-saphenous shunts offer similar hemodynamic efficiency without impacting the outcomes after liver transplantation. Their respective place and the place of portal decompression should be discussed regarding the presence of portal thrombosis and pre-existing portosystemic shunts. Evaluation of the anatomy and the efficiency of these shunts may guide tailored portal decompression., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP7) have been validated as biomarkers for acute kidney injury. We investigated the performance of both markers in predicting the occurrence and duration of functionally defined delayed graft function (fDGF) in donation after circulatory death (DCD) kidney transplant recipients., Methods: Urine samples of 74 DCD recipients were analyzed. TIMP-2 and IGFBP7 were measured with ELISA on postoperative days 1 to 7, day 10, week 6, and month 6, and values were corrected for osmolality (mOsm). Immunosuppression consisted of anti-CD25 antibody induction and triple maintenance therapy (steroids, mycophenolate mofetil, and calcineurin inhibitor). Statistical analysis included receiver operating characteristic curves and multivariate logistic regression., Results: Fifty-one (69%) renal transplant recipients had fDGF, of which 14 experienced prolonged fDGF (≥21 days). TIMP-2/mOsm on day-1 and day-10 adequately identified patients with fDGF (area under the curve [AUC], 0.91) and prolonged fDGF (AUC, 0.80), respectively, whereas IGFBP7/mOsm did not (AUC, 0.63 and 0.60). Multivariate analysis on day 1 identified 24-hour urinary creatinine excretion and TIMP-2/mOsm as significant predictors of fDGF (AUC, 0.90, 95% confidence interval, 0.80-0.98). The best predictors of prolonged fDGF on day 10 were 24-hour urinary creatinine excretion, TIMP-2/mOsm, and total warm ischemia time with an AUC of 0.85 (95% confidence interval, 0.72-0.95). Consecutive TIMP-2/mOsm values showed a decrease in TIMP-2/mOsm before an increase in estimated glomerular filtration rate, enabling us to monitor fDGF and predict resolution of fDGF., Conclusions: Urinary TIMP-2, but not IGFBP7, is a promising biomarker to predict the occurrence and duration of fDGF in DCD kidney transplant recipients.

Background: Pulmonary cuff dysfunction, either due to pulmonary vein obstruction, pulmonary vein stenosis, or pulmonary vein thrombosis, is an uncommon, yet serious complication after lung transplantation. Although there have been numerous reports of its occurrence, there is little consensus regarding the hemodynamic parameters associated with its presentation and diagnostic considerations. This systematic review summarizes the evidence surrounding pulmonary cuff dysfunction after lung transplantation surgery and empirically analyzes its implications., Methods: Databases were examined for all articles and abstracts reporting on pulmonary cuff dysfunction. Data collected included: number of patients studied; patients' characteristics; incidences of pulmonary vein stenosis and pulmonary vein thrombosis; and timing and imaging modality utilized for diagnosis., Results: Thirty-four full-text citations were included in this review. The point prevalence of pulmonary vein stenosis and thrombosis were 1.4% and 2.5%, respectively. The peak pulmonary cuff velocity associated with dysfunction was found to be 1.59 ± 0.66 m/sec. The diameter of the dysfunctional pulmonary vein was noted to be 0.48 ± 0.20 cm. The majority of diagnoses were made in the early post-operative period using transesophageal echocardiography. Overall, 41.3% of patients (26 of 63) required emergent procedural reintervention, and 32% of patients (20 of 63) diagnosed with pulmonary cuff dysfunction died during their hospital stay., Conclusions: This systematic review underscores the importance of identifying pulmonary cuff dysfunction after lung transplant surgery, and the usefulness of transesophageal echocardiography for detection of this complication. The clinical implications of these results warrant the further development of identification and management strategies for lung transplant patients., (Copyright © 2019 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Delayed graft function (DGF) is a multifactorial clinical entity. The aim of our study was to analyze the role of perioperative fluid and noninvasive hemodynamic parameters in DGF patients., Methods: The medical records of 122 adult deceased donor kidney transplant patients were retrospectively analyzed with respect to donor (medical history, kidney donor risk index), recipient (medical history), transplant (cold-warm ischemia time, renal arterial resistive index), and perioperative anesthetic, especially noninvasive hemodynamic management. Patients were grouped as DGF and immediate graft function., Results: Prevalence of DGF was 21.3% (n = 26). Delayed graft function was related to higher donor body mass index (P = .04), kidney donor risk index higher than 1.6 (P = .008), recipient age older than 65 years (P = .03), and perioperative factors, such as lower residual diuresis of recipient (8.7 [SD, 5.2] mL/kg vs 14.4 [SD, 10.3] mL/kg; P = .005), higher intradialytic weight gain (2.65 [SD, 1.03] kg vs 2.16 [SD, 0.79] kg; P = .07), and higher fluid balance during the first postoperative day (3310 [SD, 1230] mL vs 2354 [1812] mL; P = .01). The curve of change in systolic blood pressure (SBP) showed a tick mark pattern in DGF and a semicircular shape in the immediate graft function group. In the DGF group, SBP change compared with baseline value was higher at reperfusion (-3.16% [SD, 23.37%] vs -12.84% [SD, 23.37%]; P = .047), at the ending of surgery (-5.83% [SD, 26.21%] vs -3.26% [SD, 21.81%]; P = .07), and at the ending of anesthesia (11.81% [SD, 29.77%] vs -1.26% [SD, 21.87%]; P = .01). The postoperative renal arterial resistive index was higher in the DGF group (0.75 [SD, 0.10] vs 0.69 [SD, 0.08]; P = .007)., Conclusion: The tick mark pattern of SBP kinetics might help to identify DGF intraoperatively. When detecting this SBP pattern, the excessive fluid therapy should be avoided during the postoperative period to prevent iatrogenic hypervolemia leading to further graft damage., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Calcium oxalate (CaOx) deposition in the kidney may lead to loss of native renal function but little is known about the prevalence and role of CaOx deposition in transplanted kidneys., Methods: In patients transplanted in 2014 and 2015, all for-cause renal allograft biopsies obtained within 3 months post-transplantation were retrospectively investigated for CaOx deposition. Additionally, all preimplantation renal biopsies obtained in 2000 and 2001 were studied., Results: In 2014 and 2015, 388 patients were transplanted, of whom 149 had at least one for-cause renal biopsy. Twenty-six (17%) patients had CaOx deposition. In the population with CaOx deposition: Patients had significantly more often been treated with dialysis before transplantation (89 vs. 64%; p = 0.011); delayed graft function occurred more frequently (42 vs. 23%; p = 0.038); and the eGFR at the time of first biopsy was significantly worse (21 vs. 29 ml/min/1.73m2; p = 0.037). In a multivariate logistic regression analysis, eGFR at the time of first biopsy (OR 0.958, 95%-Cl: 0.924-0.993, p = 0.019), dialysis before transplantation (OR 4.868, 95%-Cl: 1.128-21.003, p = 0.034) and the time of first biopsy after transplantation (OR 1.037, 95%-Cl: 1.013-1.062, p = 0.002) were independently associated with CaOx deposition. Graft survival censored for death was significantly worse in patients with CaOx deposition (p = 0.018). In only 1 of 106 preimplantation biopsies CaOx deposition was found (0.94%)., Conclusion: CaOx deposition appears to be primarily recipient-derived and is frequently observed in for-cause renal allograft biopsies obtained within 3 months post-transplantation. It is associated with inferior renal function at the time of biopsy and worse graft survival., Competing Interests: The authors have declared that no competing interests exist.

MicroRNAs are epigenetic regulators of gene expression at the posttranscriptional level. They are involved in intercellular communication and crosstalk between different organs. As key regulators of homeostasis, their dysregulation underlies several morbidities including kidney disease. Moreover, their remarkable stability in plasma and urine makes them attractive biomarkers. Beyond biomarker studies, clinical microRNA research in nephrology in recent decades has focused on the discovery of specific microRNA signatures and the identification of novel targets for therapy and/or disease prevention. However, much of this research has produced equivocal results and there is a need for standardization and confirmation in prospective trials. This review aims to provide an overview of general concepts and available clinical evidence in both the pathophysiology and biomarker fields for the role of microRNA in AKI and kidney transplantation., (Copyright © 2019 by the American Society of Nephrology.)

Acute Tubular Injury (ATI) is the leading cause of Delayed Graft Function (DGF) after renal transplantation (RTX). Biopsies taken 1 week after RTX often show extensive tubular damage, which in most cases resolves due to the high regenerative capacity of the kidney. Not much is known about the relation between histological parameters of renal damage and regeneration immediately after RTX and renal outcome in patients with DGF. We retrospectively evaluated 94 patients with DGF due to ATI only. Biopsies were scored for morphological characteristics of renal damage (edema, casts, vacuolization, and dilatation) by three independent blinded observers. The regenerative potential was quantified by tubular cells expressing markers of proliferation (Ki67) and dedifferentiation (CD133). Parameters were related to renal function after recovery (CKD-EPI 3, 6, and 12 months posttransplantation). Quantification of morphological characteristics was reproducible among observers (Kendall's W ≥ 0.56). In a linear mixed model, edema and casts significantly associated with eGFR within the first year independently of clinical characteristics. Combined with donor age, edema and casts outperformed the Nyberg score, a well-validated clinical score to predict eGFR within the first year after transplantation (R 2  = 0.29 vs. R 2  = 0.14). Although the number of Ki67+ cells correlated to the extent of acute damage, neither CD133 nor Ki67 correlated with renal functional recovery. In conclusion, the morphological characteristics of ATI immediately after RTX correlate with graft function after DGF. Despite the crucial role of regeneration in recovery after ATI, we did not find a correlation between dedifferentiation marker CD133 or proliferation marker Ki67 and renal recovery after DGF., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

High renal resistive index (RI) is observed in diabetes and is associated with poor patient survival, but whether it is primarily due to renal vascular resistance or systemic vascular alterations is unclear. The respective impact of kidney transplant from diabetic donors or to diabetic recipients on RI would shed some light on this issue. The objective of the study was to analyze the impact of donor and recipient diabetes on RI in order to understand the respective impact of the kidney and the vascular environment. The authors conducted a retrospective study in 1827 renal transplant recipients who received a kidney between 1985 and 2017, and had Doppler measurements at 3 months after transplant. Donor and recipient characteristics at the time of transplant and at 3 months were reviewed. Both donor diabetes and recipient diabetes were associated with RI in univariate analysis, but only recipient diabetes remained significantly associated in stepwise multivariate analyses (effect estimate on RI: +0.03 ± 0.005, P < 0.001). These findings were confirmed when RI was expressed as a binary variable using a cutoff of 0.75 (OR = 2.50 [1.77, 3.54], P < 0.001). Other determinants of RI were recipient characteristics (age, sex, systolic and diastolic blood pressure, and duration of dialysis). Donor characteristics were not associated with RI. Our results suggest that high RI observed in diabetic recipients shortly after transplant is primarily due to the new vascular environment, rather than to characteristics of the transplanted kidney. Therefore, RI reflects systemic rather than intra-renal changes., (©2019 Wiley Periodicals, Inc.)

Background: Early markers to predict delayed kidney graft function (DGF) may support clinical management. We studied the ability of four biomarkers (neutrophil gelatinase associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), cystatin C, and YKL-40) to predict DGF after deceased donor transplantation, and their association with early graft function and GFR at three and twelve months., Methods: 225 deceased donor kidney transplant recipients were included. Biomarkers were measured using automated assays or ELISA. We calculated their ability to predict the need for dialysis post-transplant and correlated with the estimated time to a 50% reduction in plasma creatinine (tCr50), measured glomerular filtration rate (mGFR) and estimated GFR (eGFR)., Results: All biomarkers measured at Day 1, except urinary L-FABP, significantly correlated with tCr50 and mGFR at Day 5. Plasma NGAL at Day 1 and a timed urine output predicted DGF (AUC = 0.91 and AUC 0.98). Nil or only weak correlations were identified between early biomarker levels and mGFR or eGFR at three or twelve months., Conclusion: High plasma NGAL at Day 1 predicts DGF and is associated with initial graft function, but may not prove better than P-creatinine or a timed urine output. Early biomarker levels do not correlate with one-year graft function., Trial Registration: ClinicalTrials.gov NCT01395719., Competing Interests: The authors have declared that no competing interests exist.

Background: The problem of organ shortage is an important issue in kidney transplantation, but the effect of kidney donation on AKI is unclear. The aim of this study was to investigate the impact of acute kidney injury (AKI) on post-transplant clinical outcomes for deceased donor kidney transplantation (DDKT) using standard criteria donors (SCDs) versus expanded criteria donors (ECDs)., Methods: Five-hundred nine KT recipients receiving kidneys from 386 deceased donors (DDs) were included from three transplant centers. Recipients were classified into the SCD-KT or ECD-KT group according to corresponding DDs and both groups were divided into the AKI-KT or non-AKI-KT subgroups according to AKI in donor. We compared the clinical outcomes among those four groups and investigated the interaction between AKI in donors and ECD on allograft outcome., Results: The incidence of delayed allograft function was higher when the donors had AKI within SCD-KT and ECD-KT groups. In allograft biopsies within 3 months, chronic change was more significant in the AKI-ECD-KT subgroup than in the non-AKI-ECD-KT subgroup, but it did not differ between AKI-SCD-KT and non-AKI-SCD-KT group. AKI-ECD-KT showed higher risk for death-censored allograft failure than the other three groups and a significant interaction was observed between AKI in donors and ECD on the allograft outcome., Conclusions: The presence of AKI in ECDs significantly impacted the long-term allograft outcomes of kidney transplant recipients, but it did not in SCDs.

Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplant (KT) with short-term outcomes similar to those obtained from donation after brain death (DBD) donors. However, heterogeneous results in the long term have been reported. We compared 10-year outcomes between 237 KT recipients from uDCD donors maintained by normothermic extracorporeal membrane oxygenation (nECMO) and 237 patients undergoing KT from standard criteria DBD donors during the same period at our institution. We further analyzed risk factors for death-censored graft survival in the uDCD group. Delayed graft function (DGF) was more common in the uDCD group (73.4% vs 46.4%; P < .01), although glomerular filtration rates at the end of follow-up were similar in the 2 groups. uDCD and DBD groups had similar rates for 10-year death-censored graft (82.1% vs 80.4%; P = .623) and recipient survival (86.2% vs 87.6%; P = .454). Donor age >50 years was associated with graft loss in the uDCD group (hazard ratio: 1.91; P = .058), whereas the occurrence of DGF showed no significant effect. uDCD KT under nECMO support resulted in similar graft function and long-term outcomes compared with KT from standard criteria DBD donors. Increased donor age could negatively affect graft survival after uDCD donation., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: We present our experience with hypothermic machine perfusion (HMP) versus cold storage (CS) in relation to kidney transplant outcomes., Methods: Retrospective analysis of 33 consecutive HMP kidney transplant outcomes matched with those of 33 cold stored: delayed graft function (DGF), length of hospital stay (LOS), estimated glomerular filtration rate (eGFR), and patient and graft survival were compared. Renal Resistive Indexes (RIs) during HMP in relation to DGF were also analysed., Results: In the HMP group, mean HMP time was 5.7 ± 3.9 hours with a mean cold ischaemic time (CIT) of 15 ± 5.6 versus 15.1 ± 5.3 hours in the CS group. DGF was lower in the HMP group (p=0.041), and donation after Circulatory Death (DCD) was a predictor for DGF (p<0.01). HMP decreased DGF in DCD grafts (p=0.036). Patient and graft survival were similar, but eGFR at 365 days was higher in the HMP cohort (p<0.001). RIs decreased during HMP (p<0.01); 2-hours RI ≥ 0.45 mmHg/mL/min predicted DGF in DCD kidneys (75% sensitivity, 80% specificity; area under the curve 0.78); 2-hours RI ≥ 0.2 mmHg/ml/min predicted DGF in DBD grafts (sensitivity 100%, specificity 91%; area under the curve 0.87)., Conclusion: HMP decreased DGF compared to CS, offering viability assessment pretransplant and improving one-year renal function of the grafts.

Aim: Differences in early graft function between kidney transplant recipients previously managed with either haemodialysis (HD) or peritoneal dialysis are well described. However, only two single-centre studies have compared graft and patient outcomes between extended hour and conventional HD patients, with conflicting results., Methods: This study compared the outcomes of all extended hour (≥24 h/week) and conventional HD patients transplanted in Australia and New Zealand between 2000 and 2014. The primary outcome was delayed graft function (DGF), defined in an ordinal manner as either a spontaneous fall in serum creatinine of less than 10% within 24 h, or the need for dialysis within 72 h following transplantation. Secondary outcomes included the requirement for dialysis within 72 h post-transplant, acute rejection, estimated glomerular filtration rate at 12 months, death-censored graft failure, all-cause and cardiovascular mortality, and a composite of graft failure and mortality., Results: A total of 4935 HD patients (378 extended hour HD, 4557 conventional HD) received a kidney transplant during the study period. Extended hour HD was associated with an increased likelihood of DGF compared with conventional HD (adjusted proportional odds ratio 1.33; 95% confidence interval 1.06-1.67). There was no significant difference between extended hour and conventional HD in terms of any of the secondary outcomes., Conclusion: Compared to conventional HD, extended hour HD was associated with DGF, although long-term graft and patient outcomes were not different., (© 2018 Asian Pacific Society of Nephrology.)

Background: resistive index (RI) is highly utilised to assess the graft function using Doppler ultrasonography. The RI has been shown as the best ultrasound parameter to assess kidney allograft dysfunction. Several studies have established the role of the RI as a predictor of transplant failure. However, these studies were using RI measurement in the later stages post transplantation. The present study has conducted to identify the association between early RI measurement and early graft function represented as delayed graft function (DGF) and immediate graft function (IGF), as well as long-term graft survival., Methods: an evidence-based clinical review of studies published before May 2018 was conducted from Medline, Science Direct, EMBASE and Cochrane databases. Studies on early measurement of RI whereby the primary or secondary goals of the study related to graft function and/or graft survival were included. Studies using late RI measurement and without RI value groups were excluded. The Mantzel-Haenzel method was used to analyse pooled risk ratio and 95% confidence interval, while the heterogeneity of the study was calculated through I2 value. Data analysis was performed using Review Manager 5.3., Results: nine studies with a total of 1802 patients who had undergone a kidney transplant were analysed. DGF was found in 19% (193/1015) of the low RI group and in 42.8% (337/787) of the high RI group (RR 2.04 (95% CI 1.72 - 2.41), p < 0.00001, I2 = 28%). IGF was found in 39.5% (62/157) of the low RI group and in 10.5% (28/268) of the high RI group (RR 0.26 (95% CI 0.17 - 0.40), p < 0.00001, I2 = 0%). Long-term graft survival, with follow up between 60-144 months, was found in 83% (701/845) of the low RI group and in 69.4% (395/569) of the high RI group (RR 0.82 (95% CI 0.72 - 0.93), p = 0.002, I2 = 63%)., Conclusion: the results of this study emphasise the association between early measurement of RI and early graft function, and long-term graft survival. An elevated RI provides the chance of recognizing the patients with poor long-term prognosis, from the first moment after kidney transplant.